Protective Effects and Mechanisms of Active Fractions of Ixeris sonchifolia on Rats With Toxic Heat and Blood Stasis Syndrome Revealed by Pharmacodynamics and Metabonomics

ABSTRACT Ixeris sonchifolia (IS) has been demonstrated to have beneficial effects on clearing heat and detoxifying, promoting blood circulation and removing blood stasis. However, the protective effects of active fractions and the underlying mechanisms of IS against toxic heat and blood stasis syndrome (THBSS) remain unclear. This study aimed to investigate this. In this study, the protective effects of 30%, 50%, and 70% ethanol fractions of IS on rats with THBSS were evaluated by observing myocardial pathology, analyzing blood rheology and blood routine indices, and the general conditions of the rats. Comprehensive metabolomic analysis of plasma and myocardium samples was conducted using ultra‐high‐performance liquid chromatography linear ion trap quadrupole orbitrap mass spectrometry (UHPLC‐LTQ‐Orbitrap MS/MS). The results showed that IS‐30% had a significant protective effect on rats with THBSS, and it could play a protective role by modulating 35 differential metabolites associated with key metabolic pathways, including glycerophospholipid metabolism, sphingosine metabolism, alpha‐linolenic acid metabolism, and nicotinate and nicotinamide metabolism. Analysis of different metabolites and pathways showed that they are closely associated with inflammatory responses; therefore, it is hypothesized that IS‐30% may protect against THBSS by exerting an anti‐inflammatory effect. This study provides valuable data supporting the druggability of IS‐30% and offers new insights into its potential therapeutic applications.